The present invention relates to a liquid chromatography/mass spectrometry apparatus. More specifically, it relates to a liquid chromatography/mass spectrometry apparatus which combines a liquid chromatograph having a liquid delivery part for performing gradient delivery with mixed multiple solvents, and a mass spectrometry device having an atmospheric pressure ionization interface for ionizing sample components by spraying a liquid sample in a roughly atmospheric-pressure atmosphere.
As one analytical means of a liquid chromatograph, there is the gradient delivery method. In this method, multiple solvents having different natures, for example, water and organic solvent, are mixed. The mobile phase liquid is delivered to the column while changing the ratio of the mixture over the passage of time, and it is particularly useful for performing separation into components of samples containing multiple components.
A liquid chromatography/mass spectrometry apparatus (abbreviated below as “LC/MS”), which uses a mass spectrometry device as a detector for such a liquid chromatograph for performing gradient delivery, is known. See, for example, Japanese Unexamined Patent Publication No. H11-326302.
Generally in an LC/MS, an atmospheric-pressure ionization interface is used in order to generate gaseous ions from component molecules in the elution from the column. As representatives of atmospheric-pressure ionization interfaces, there are electro-spray ionization interface (ESI) and atmospheric-pressure chemical ionization interface (APCI), and the like. Both of these have a nozzle for spraying the elution from the column into a roughly atmospheric-pressure atmosphere.
In ESI, a biased charge is applied to a liquid sample when spraying the sample. Making the droplets microscopic is promoted by coulomb repulsion within the sprayed droplets, and in that process the object components within the droplets are ionized.
On the other hand, in APCI, an electrostatic electrode is placed in front of the nozzle, and the object components are ionized by chemically reacting solvent gas ions generated by the corona discharge with the microscopic droplets.
In either case, in such an ionization interface, the spray state of the droplets from the nozzle greatly influences the ionization efficiency, and the value of the applied voltage, which is one of the factors determining the spray state, is one important parameter. However, in the conventional LC/MS, it is common that the applied voltage is fixed at a voltage thought to be nearly optimal.
In an LC/MS for performing the above-mentioned gradient delivery, the MS operating condition uses an optimal value obtained when adjusted under a water/organic solvent condition at a certain mixture ratio. Meanwhile, it is often the case that the optimal value of the applied voltage is provided in advance by the device manufacturer for each device type. But because this voltage value can be changed by the user, for example, in the case when a component eluted under a condition of high organic solvent ratio is important, it is naturally proper to use an optimal value obtained under a mobile phase condition of high organic solvent ratio.
For example, in the case when using ESI as the ionization interface and the MS operating condition is automatically adjusted in the above-described manner, a fixed voltage is applied to the nozzle of the ionization part during analysis by gradient delivery. However, because the spray state of the liquid sample from the nozzle is also dependent on various properties of the mobile phase liquid, for example polarity, viscosity, and the like, it is subject to the influence not only of the type of solvent, but also its mixture ratio, and the like.
Therefore, when the mixture ratio of the solvent changes over the passage of time by gradient delivery, even if the ionization efficiency of the ionization interface was optimal at a certain time (or time period) during analysis, it does not become optimal at other time periods, and at those times, the detection sensitivity also is lowered. As a result, there is a problem that analysis cannot be performed with the highest, or nearly highest, detection sensitivity for all of the multiple components contained in the sample. Thus, one is forced to sacrifice sensitivity when analyzing several components.
It is also often the case that an issue such as that described above does not become so significant a problem with an ESI having a comparatively high flow volume, which is commonly used. As a matter of fact, in nano-ESI, which recently has been widely used in the biochemical field and the like, because the flow volume is as little as 1/100˜1/1000 of the conventional volume, a problem such as that described above appears very prominently. Therefore, in extreme cases, it may also be that several of the multiple components contained in a sample cannot be substantially analyzed.
The present invention was created in consideration of the above-described problems. An object of the invention, therefore, is to provide a liquid chromatography/mass spectrometry apparatus in which the ionization efficiency of the ionization interface can always be maintained at a high level.
Another object of the invention is to provide a liquid chromatography/mass spectrometry apparatus in which high-sensitivity analysis of multiple components can be performed, even in the case where the mixture ratio of the solvent changes gradually over the passage of time by gradient delivery.
Further objects and advantages, of the invention will be apparent from the following description of the invention.